The purpose of this project is to optimize effective therapy for patients with peritoneal involvement of ovarian cancer using regional radioimmunotherapy. These studies will utilize a newly designed recombinant monoclonal antibody with a deleted Ch2 region (HuCC49 Ch2) radiolabeled with 188Re and administered by the intraperitoneal route (IP). Their prior phase I studies with 177Lu-CC49 have shown evidence of antitumor effects (objective responses and prolonged disease-free survival) but the trials were limited by the immunogenicity of the murine monoclonal antibody and dose-limiting marrow suppression. The newly designed molecule should have little or no immunogenicity allowing repeated courses of therapy. Also, animal studies have confirmed the predicted improved tumor penetration and short plasma half-life due, in part, to the small size of the antibody construct. The construct will be radiolabeled with 188Re, which has shown superior results in animal studies and is predicted to reduce marrow radiation in analysis of clinical data. This new radiolabeled product 188Re-HuCC49 Ch2 will be possible due to availability of 188Re from a generator and a stable trisuccin chelator synthesized and tested by their team. Their initial phase I trial will establish the maximum tolerated dose (MTD) or 188Re-HuCC49 Ch2 administered by IP route and include studies of immune response, imaging, dosimetry, pharmacokinetics, tumor response, and tumor markers. Dr. Donald Buchsbaum will concurrently analyze repeat dose schedules and integration of radiosensitizing agents in animal models. The animal model results will be utilized in the design of subsequent clinical trial aimed to estimate response rate or to further improve the antitumor effects of IP radioimmunotherapy with 188Re-HuCC49 Ch2. These studies should provide effective new therapy for ovarian cancer patients who have relapsed after standard therapy or possibly as an adjuvant strategy in first-line therapy.